Lipoperoxidação, perda de viabilidade celular e diminuição da liberação de IL-8 de neutrófilos humanos na presença de corpos cetônicos

• Autor(a) principal: Gileno, M. C. [UNESP]
• Data de Publicação: 2009
• Outros Autores: Ximenes, Valdecir Farias [UNESP], Da Fonseca, Luiz Marcos [UNESP]
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://serv-bib.fcfar.unesp.br/seer/index.php/Cien_Farm/article/view/1281; http://hdl.handle.net/11449/71138
• topic: Acetoacetate; Diabetes mellitus; Interleukine-8; Lipoperoxidation; Neutrophils; 3 hydroxybutyric acid; acetoacetic acid; interleukin 8; ketone body; lactate dehydrogenase; thiobarbituric acid reactive substance; zymosan; acidosis; cell culture; cell loss; cell viability; cytokine release; cytotoxicity; enzyme linked immunosorbent assay; fatty acid metabolism; human; incubation temperature; insulin dependent diabetes mellitus; lipid peroxidation; neutrophil

Type-1 diabetes patients suffer from frequent episodes of acidosis caused by an increased fatty acid metabolism and consequently increased plasma level of acetoacetate (AcAc) and β-hydroxybutyrate (β-HOB). This article describes a study of the effects of pathological concentrations of AcAc and β-HOB on lipoperoxidation, cell viability and the release of the CXCL8 (IL-8) cytokine by activated neutrophils. Neutrophils from healthy donors were isolated by density gradient (Histopaque® 1077/1119) and incubated with the ketone bodies. Lipoperoxidation was determined as thiobarbituric acid reactive substances (TBARS). The cell viability was evaluated by the release of intracellular lactate dehydrogenase. The release of CXCL8 was measured by ELISA in a 24-h culture of opsonized zymosan-stimulated neutrophils. AcAc, but not β-HOB, provoked a dose-dependent increase in the neutrophil membrane lipoperoxidation (p<0.05; r =0.9915). In the cytotoxicity assay, a dose-dependent release of LDH was observed when the neutrophils were incubated with AcAc in concentrations up to 40 mM (p<0.05). β-HOB was devoid of effect. The release of CXCL8 was inhibited by AcAc and β-HOB in a dose-dependent manner. In conclusion, these results suggest that the accumulation of ketone bodies in diabetic patients could be involved in their usually increased susceptibility to infection.